Purpose: To study the linear energy transfer (LET) effect upon rib fracture (RF) in breast cancer patients treated with pencil-beam-scanning proton therapy (PBS) using dose-LET volume histogram (DLVH).
Methods: We retrospectively identified RF cases in breast cancer patients treated with PBS to the breast/chest wall and regional nodes from 2015-2020. Control patients were selected to match the RF patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year. For all plans, a chest wall was contoured. Both dose and LET were calculated using a Monte-Carlo engine. DLVH was generated for each patient. The DLVH index, V(d, l), defined as V(% for normalized volume) of the structure with a dose of at least d Gy[RBE] and an LET of at least l keV/µm, was calculated for all combinations of d and l. Conditional logistic regression was used to establish the relation of V(d, l) and the observed RF at each combination of d and l. The derived p-values constitute a p-value map in the dose and LET plane. Concordance and its standard error (se) map were generated to evaluate the performances for all DLVH indices. Correlation coefficient maps were obtained to determine the correlation between the featured DLVH indices.
Results: Eight RF cases were identified, and 16 controls were matched. Two characteristics correlated with RF (p<0.2): 1) Smaller V(50-54Gy[RBE], 0-4.4keV/µm) of the RF patients with a maximum concordance of 0.813 (se 0.114); 2) Larger V(0-36Gy[RBE], 5.2-6.8keV/µm) of the RF patients with a maximum concordance of 0.875 (se 0.119) compared with controls. These two features were independent with a weak negative correlation (-0.185).
Conclusion: The increase of high LET in moderate dose regions of the chest wall from constraining the adjacent heart and lung dose during PBS treatment planning may result in increased risk of RF.
Funding Support, Disclosures, and Conflict of Interest: This research was supported by Arizona Biomedical Research Commission Investigator Award (ADHS16-162521), the Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, and the Kemper Marley Foundation.